Type 2 diabetes is a chronic debilitating disease that threatens to reach pandemic level by 2030. Nearly 350 million people worldwide are currently affected by diabetes and more than 70% of patients with type 2 diabetes die of cardiovascular causes. However, no particular diabetes medication to date is considered superior in the minimization of the risk of cardiovascular diseases associated with type 2 diabetes. Therefore, development of new anti-diabetic drugs that also decreases the risk of cardiovascular diseases will be highly desirable and needed. The product being developed is DT-110, a tripeptide, as an oral therapeutic for treatment of type 2 diabetes. Technological innovation is the application of tripeptide as an oral dosage form to treat human diseases. In our phase I study, we found that DT-110 activates G protein coupled receptor D (MrgprD) signaling pathway that has not been reported to be linked to metabolic diseases. Since activation of MrgprD has been shown to play a protective role in cardiovascular system, our results suggest that DT-110 may have beneficial effects on cardiovascular system in addition to controlling blood glucose levels, and therefore, potentially be a first anti-diabetic drug that can minimize the risk of cardiovascular diseases associated with type 2 diabetes. The long-term goal of this SBIR is to complete the preclinical study on DT-110, file IND, and commercialize it as a new class of anti-type 2 diabetes drugs capable of reducing the risk of cardiovascular diseases associated with type 2 diabetes. The mechanism of action of DT-110 is different from that of the currently available medications for type 2 diabetes. In the Phase II study, we will test the hypothesis that DT-110 specifically acts on this novel signaling pathway to effectively lower the blood glucose levels and protecting cardiovascular system in the patients with type 2 diabetes. Specific aims of this Phase II SBIR are 1) to examine the therapeutic roles of DT-110 in controlling glucose levels and in regulation of blood vessel vasodilation in the genetically modified mice, 2) to develop an enteric coated DT-110, and 3) to determine the blood glucose lowering effect of DT-110 in a large animal model. This study will provide significant information for our understanding of novel mechanism of action of DT-110 and its efficacy in various animal models to support IND filing, and ultimately lead to successful development of a new drug for treatment of type 2 diabetes, which may also has a protective effect on cardiovascular system.